AGER advanced glycosylation end-product specific receptor
ENSG00000204305 · protein coding · Open Targets profile
Cell surface pattern recognition receptor that senses endogenous stress signals with a broad ligand repertoire including advanced glycation end products, S100 proteins, high-mobility group box 1 protein/HMGB1, amyloid beta/APP oligomers, nucleic acids, histones, phospholipids and glycosaminoglycans (PubMed:27572515, PubMed:28515150, PubMed:34743181, PubMed:35974093, PubMed:24081950). Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes (PubMed:21565706). These ligands accumulate at inflammatory sites during the pathogenesis of various diseases including diabetes, vascular complications, neurodegenerative disorders and cancers, and RAGE transduces their binding into pro-inflammatory responses. Upon ligand binding, uses TIRAP and MYD88 as adapters to transduce the signal ultimately leading to the induction of inflammatory cytokines IL6, IL8 and TNFalpha through activation of NF-kappa-B (PubMed:21829704, PubMed:33436632). Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key pro-inflammatory mediators (PubMed:19386136). Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Contributes to the translocation of amyloid- beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons (PubMed:19906677). ABPP- initiated RAGE signaling, especially stimulation of p38 mitogen- activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Participates in endothelial albumin transcytosis together with HMGB1 through the RAGE/SRC/Caveolin-1 pathway, leading to endothelial hyperpermeability (PubMed:27572515). Mediates the loading of HMGB1 in extracellular vesicles (EVs) that shuttle HMGB1 to hepatocytes by transferrin-mediated endocytosis and subsequently promote hepatocyte pyroptosis by activating the NLRP3 inflammasome (PubMed:34743181). Binds to DNA and promotes extracellular hypomethylated DNA (CpG DNA) uptake by cells via the endosomal route to activate inflammatory responses (PubMed:24081950, PubMed:28515150). Mediates phagocytosis by non-professional phagocytes (NPP) and this is enhanced by binding to ligands including RNA, DNA, HMGB1 and histones (PubMed:35974093). Promotes NPP-mediated phagocytosis of Saccharomyces cerevisiae spores by binding to RNA attached to the spore wall (PubMed:35974093). Also promotes NPP-mediated phagocytosis of apoptotic cells (PubMed:35974093). Following DNA damage, recruited to DNA double-strand break sites where it colocalizes with the MRN repair complex via interaction with double-strand break repair protein MRE11 (By similarity). Enhances the endonuclease activity of MRE11, promoting the end resection of damaged DNA (By similarity). Promotes DNA damage repair in trophoblasts which enhances trophoblast invasion and contributes to placental development and maintenance (PubMed:33918759). Protects cells from DNA replication stress by localizing to damaged replication forks where it stabilizes the MCM2-7 complex and promotes faithful progression of the replication fork (PubMed:36807739). Mediates the production of reactive oxygen species (ROS) in human endothelial cells (PubMed:25401185). {ECO:0000250|UniProtKB:Q62151, ECO:0000269|PubMed:19906677, ECO:0000269|PubMed:20943659, ECO:0000269|PubMed:21559403, ECO:0000269|PubMed:21565706, ECO:0000269|PubMed:21829704, ECO:0000269|PubMed:24081950, ECO:0000269|PubMed:25401185, ECO:0000269|PubMed:27572515, ECO:0000269|PubMed:28515150, ECO:0000269|PubMed:33436632, ECO:0000269|PubMed:33918759, ECO:0000269|PubMed:34743181, ECO:0000269|PubMed:35974093, ECO:0000269|PubMed:36807739}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.9422000050544739 (upper bound 1.204699993133545). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 12 registry trials, updated in the last three years, of the most advanced drugs against AGER (azeliragon), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Akshitkumar M MistryUofL Health - Brown Cancer Center · 1 of 1 trials Phase 2+
- Andrew HendifarCedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute · 1 of 1 trials Phase 2+
- Candace MainorGeorgetown University · 1 of 1 trials Phase 2+
- Juan SepúlvedaHospital Universitario 12 de Octubre · 1 of 1 trials Phase 2+
- Lucas S. BlantonUniversity of Texas · 1 of 1 trials Phase 2+
- Minesh MehtaMiami Cancer Institute at Baptist Health, Inc. · 1 of 1 trials Phase 2+
- Stephen G MarcusCantex Pharmaceuticals · 1 of 1 trials Phase 2+
- Jana L PortnowCity of Hope Medical Center · 0 of 1 trials Phase 2+
- Jiayi HuangWashington University School of Medicine · 0 of 1 trials Phase 2+
- Jonathan YangNYU Langone Health · 0 of 1 trials Phase 2+
Registry trials of azeliragon updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 10 of 10 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
5 trials of drugs against AGER were stopped early
Terminated, withdrawn and suspended interventional trials of azeliragon, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 5 most recent of 5.
- suspended · 2026-06-16 · Baptist Health South Florida · Azeliragon“Funding”
- withdrawn · 2024-09-19 · City of Hope Medical Center · Azeliragon“Funding”
- terminated · 2022-01-21 · vTv Therapeutics · Azeliragon“for business reasons”
- terminated · 2021-06-01 · vTv Therapeutics · Azeliragon 5mg“Not due to safety but due to a lack of efficacy at the 5 mg azeliragon dose.”
- terminated · 2021-05-07 · vTv Therapeutics · Azeliragon“Not due to safety but due to a lack of efficacy at the 5 mg azeliragon dose.”
Paediatric incentives and obligations for AGER's drugs
For azeliragon: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · AGER is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names azeliragonRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names azeliragonRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of azeliragonRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of azeliragonRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: no · No interventional study of azeliragon includes patients under 18Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 1 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| AZELIRAGON | Small molecule | phase 3 | Alzheimer disease, pneumonia, COVID-19, diabetic kidney disease, glioblastoma, cardiotoxicity, Mental deterioration, pancreatic neoplasm, +4 more | Open Targets · ChEMBL |